Methods for classifying and treating breast cancers

Abstract

The present invention relates to methods of treating a breast cancer in a subject, methods of identifying a subject with a breast cancer as a candidate for a therapy having efficacy for treating a breast cancer molecular subtype, and methods of selecting a therapy for a subject with a breast cancer. The methods comprise determining the molecular subtype of the breast cancer in the subject. In some embodiments, the methods further comprise administering to the subject a therapy that is effective for treating the molecular subtype of the breast cancer.

1 . A method of treating a breast cancer in a subject, comprising:
 a) determining the molecular subtype of the breast cancer in the subject, wherein the molecular subtype is selected from the group consisting of a molecular subtype I breast cancer, a molecular subtype II breast cancer, a molecular subtype III breast cancer, a molecular subtype IV breast cancer, a molecular subtype V breast cancer and a molecular subtype VI breast cancer; and   b) administering to the subject a therapy that is effective for treating the molecular subtype of the breast cancer determined in step a).   
     
     
         2 . The method of  claim 1 , wherein the molecular subtype of the breast cancer is molecular subtype I and a therapy that includes an adjuvant chemotherapy is administered to the subject. 
     
     
         3 . The method of  claim 2 , wherein the adjuvant chemotherapy comprises administering methotrexate, wherein before determining the molecular subtype of the breast cancer in the subject, the subject was a candidate for receiving an adjuvant chemotherapy comprising anthracycline and after determining the molecular subtype of the breast cancer in the subject, anthracycline is not administered to the subject. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the molecular subtype of the breast cancer is molecular subtype II and a therapy that includes at least one member selected from the group consisting of administration of a HER2/EGFR signaling pathway antagonist, a high intensity chemotherapy and a dose-dense chemotherapy is administered to the subject. 
     
     
         6 . The method of  claim 5 , wherein the therapy comprises administering a HER2/EGFR signaling pathway antagonist. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the breast cancer is a molecular subtype I or a molecular subtype II, and wherein the method further comprises determining an immune response score, wherein adjuvant chemotherapy is administered to a subject with a low immune response score. 
     
     
         9 . The method of  claim 8 , wherein the breast cancer is a molecular subtype I and the therapy comprises adjuvant chemotherapy comprising anthracycline. 
     
     
         10 . The method of  claim 1 , wherein the molecular subtype of the breast cancer is selected from the group consisting of molecular subtype III and molecular subtype VI and a therapy that includes at least one anti-estrogen therapy is administered to the subject. 
     
     
         11 . The method of  claim 1 , wherein the molecular subtype of the breast cancer is molecular subtype IV and a therapy that includes an adjuvant chemotherapy comprising at least one anthracycline is administered to the subject. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 11 , wherein before determining the molecular subtype of the breast cancer in the subject the subject is a candidate for adjuvant chemotherapy comprising administering methotrexate and after determining the molecular subtype of the breast cancer in the subject, anthracycline is administered to the subject. 
     
     
         14 . The method of  claim 11 , wherein before determining the molecular subtype of the breast cancer in the subject the subject is a candidate for adjuvant chemotherapy comprising administering a HER2/EGFR signaling pathway antagonist and after determining the molecular subtype of the breast cancer in the subject, a HER2/EGFR signaling pathway antagonist is not administered to the subject. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the molecular subtype of the breast cancer is molecular subtype V and a therapy that includes anti-estrogen therapy is administered to the subject. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 17 , wherein before determining the molecular subtype of the breast cancer in the subject the subject is a candidate for adjuvant chemotherapy and after determining the molecular subtype of the breast cancer in the subject, the subject is not administered adjuvant chemotherapy. 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein before determining the molecular subtype of the breast cancer in the subject, the subject is a candidate for adjuvant chemotherapy. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 22 , wherein an adjuvant chemotherapy is not administered to the subject. 
     
     
         25 . A method of identifying a subject with a breast cancer as a candidate for a therapy having efficacy for treating a breast cancer molecular subtype, comprising:
 a) determining the molecular subtype of the breast cancer in the subject, wherein the molecular subtype is selected from the group consisting of a molecular subtype I breast cancer, a molecular subtype II breast cancer, a molecular subtype III breast cancer, a molecular subtype IV breast cancer, a molecular subtype V breast cancer and a molecular subtype VI breast cancer; and   b) identifying the subject as a candidate for a therapy that is effective for treating the molecular subtype determined in step a).   
     
     
         26 .- 30 . (canceled) 
     
     
         31 . A method of selecting a therapy for a breast cancer in a subject, comprising:
 a) determining the molecular subtype of the breast cancer in the subject, wherein the molecular subtype is selected from the group consisting of a molecular subtype I breast cancer, a molecular subtype II breast cancer, a molecular subtype III breast cancer, a molecular subtype IV breast cancer, a molecular subtype V breast cancer and a molecular subtype VI breast cancer; and   b) selecting a therapy that is effective for treating the molecular subtype determined in step a).   
     
     
         32 .- 36 . (canceled) 
     
     
         37 . A method of classifying a breast cancer, comprising:
 a. comparing the gene expression profile of the breast cancer to one or more reference gene expression profiles for a breast cancer molecular subtype selected from the group consisting of a molecular subtype I breast cancer, a molecular subtype II breast cancer, a molecular subtype III breast cancer, a molecular subtype IV breast cancer, a molecular subtype V breast cancer and a molecular subtype VI breast cancer; and   b. classifying the breast cancer as a molecular subtype I breast cancer, a molecular subtype II breast cancer, a molecular subtype III breast cancer, a molecular subtype IV breast cancer, a molecular subtype V breast cancer or a molecular subtype VI breast cancer.   
     
     
         38 . The method of  claim 37 , wherein the gene expression profile is generated from the expression level of at least about 30% of the genes in Table I. 
     
     
         39 .- 47 . (canceled) 
     
     
         48 . A method of prognosing a subject suspected of having breast cancer for one or more clinical indicators, comprising the steps of the method of classifying a breast cancer of  claim 37 , wherein the prognosis is based on the classification step (b) and wherein the one or more clinical indicators are selected from the group consisting of metastasis risk, T stage, TNM stage, metastasis-free survival, and overall survival. 
     
     
         49 . The method of  claim 48 , further comprising determining the immune response score of the subject, wherein a low immune response score indicates reduced metastasis-free survival.